ABSTRACT OF RESEARCH PLAN FOR MERIT EXTENSION (lALONGO, R37 DA11796) The central purpose of this MERIT extension is to extend through age 25 an examination of normal and pathogenic development and the impact of two, universal, first grade, preventive interventions on the distal targets of antisocial behavior, substance abuse/dependence, psychiatric symptoms/disorders, and successful adaptation to the relevant developmental demands of the educational, work, peer group, romantic relationships, and family (both family of procreation and origin/orientation) socialfields/contexts.This application capitalizes on the scientific value of two ongoing studies: 1) a prospective, developmental epidemiological prevention trial involving a population (N = 798) of urban, predominately African-American youth, who begin first grade in the fall of 1993 in 9 elementary schools in predominantiy low to lower middle-income Baltimore areas (lalongo et al., 1999) and 2) an ongoing study of allelic variants (Uhl et al., 2007, 2008) that predispose to addiction vulnerability in research volunteers drawn from many of the same Baltimore neiglnborhoods. Participants in the epidemiological prevention trial sample were randomly assigned to one of two universal, elementary school-based, preventive interventions (Classroom- Centered, CC, and Family-School Partnership, FSP), which targeted antecedents of later substance use/abuse/dependence, antisocial behavior, anxiety and depression: 1) aggressive/disruptive behaviors, and 2) poor school achievement Annual data on mental health, educational, substance use, abuse, and dependence outcomes and the hypothesized moderators and mediators ofthese outcomes (including youth, family, peer group, school, and neighborhood characteristics) have been collected from 1(R)' grade through age 21. Participants in the ongoing study of allelic variants among research volunteers that predispose to addiction vulnerability have had more than 500,000 SNP allelic frequencies determined in African-American samples. In this application, we are requesting funds to extend through age 25 the annual follow-up assessments of antisocial behavior, psychiatric symptoms/disorders, substance abuse and dependence, and successful adaptation to the relevant developmental demands of the educational, work, peer group, romantic relationships, and family social fields/domains. We are also requesting funds to annually assess the moderators and mediators ofthese developmental and inten/ention outcomes, along with mental health and drug treatment services utilization and the factors associated with unmet mental health and drug treatment need. The requested funds would also allow for a continued collaboration between the JHU investigative team and Dr. George Uhl of the NIDA-IRP Molecular Neurobiology Branch to study candidate gene and candidate genomic markers of substance dependence in the well-characterized participants in our developmental epidemiological prevention trial population. Dr Uhl's laboratory has identified markers for allelic variants that display nominally-significant differences in terms of substance dependence between both European- and African-American samples of research volunteers who come from many of the same Baltimore area zip codes as the members of our current prevention trail sample. In his laboratory's studies of DNAs from more than 1250 individuals with the outlying phenotypes, he has assessed allelic frequencies of more than 500,000 SNP markers in studies of more than 200 million genotypes. With this data In hand. Dr Uhl can identify genomic markers that are likely to reproducibly distinguish substance dependent individual from control individuals in Baltimore populations. These underlying data are thus likely to provide some of the best genomic controls currently possible to avoid stratification artifacts, the major problem with association genetic studies that might otherwise be a significant issue with the admixed African-American populations identified in US urban centers. The knowledge gained over tfie life of the proposed research should serve to inform the field as to (a) for whom these universal interventions work as a function of their pheno- and genotypic characteristics, (b) to what degree, (c) for how long, (d) in what contexts, (e) what else is needed in terms of mental health or drug treatment services or preventive interventions (e.g., selective interventions or indicated interventions), and (f) when in the elementary, middle, high school, and early adult years these additional interventions should be implemented. The unique scientific opportunities the proposed study provides are reflected in our specific aims: 1. Modeling Intervention Impact and Variation In Developmental & Intervention Outcomes. To assess intervention outcomes through age 25 to determine the extent to which genetic factors influence variation in inten/ention outcomes through youth and family characteristics. To examine possible roles of interventions as well as family, peer group, school, and neighborhood factors as moderators of potential genetic effects, seeking specific gene x environment interactions.. 2. Assessing the Incidence, Prevalence. & Antecedents of Emerging Mental and Substance Disorders. To use genotypes from blood or buccal/salivary samples to model genetic influences on the onset, course and comorbidity of psychiatric symptoms and disorders and substance use, abuse, and dependence through youth and family characteristics from 1' grade to age 25. To examine the potential roles of family, peer group, school and neighborhood factors as moderators of potential genetic effects (gene x environment Interactions) on the onset, course, and comorbidity of psychiatric symptoms and disorders and substance use, abuse, and dependence. 3. Assessing the Degree of Unmet Need and the Factors Associated with It To assess the degree of unmet mental health and drug treatment need and the factors associated with it. This knowledge should determine the need for interventions aimed at improving sen/ice utilization among urban, economically disadvantaged, African- American, young adults, and the factors targeted by those interventions.